DNA-based prenatal diagnosis of plectin-deficient epidermolysis bullosa simplex associated with pyloric atresia.

Abstract

BACKGROUND:

Mutations in the plectin gene (PLEC) generally lead to epidermolysis bullosa simplex (EBS) associated with muscular dystrophy. It has been recently demonstrated that PLEC mutations can also cause a different clinical subtype, EBS associated with pyloric atresia (EBS-PA), which shows early lethality. Prenatal diagnosis (PND) of EBS-PA using mutation screening of PLEC has not been described.

OBJECTIVE:

This study aimed to perform DNA-based PND for an EBS-PA family.

MATERIALS AND METHODS:

The EBS-PA proband was compound-heterozygous for a paternal c.1350G>A splice-site mutation and a maternal p.Q305X nonsense mutation. Genomic DNA was obtained from amniocytes taken from an at-risk fetus of the proband's family. Direct sequencing and restriction enzyme digestion of polymerase chain reaction products from the genomic DNA were performed.

RESULTS:

Mutational analysis showed that the fetus harbored both pathogenic mutations, suggesting that the fetus was a compound-heterozygote and therefore affected with EBS-PA. The skin sample obtained by autopsy from the abortus confirmed the absence of plectin expression at the dermal-epidermal junction.

CONCLUSIONS:

This is the first successful DNA-based PND for an EBA-PA family.

• Authors: Hideki Nakamura, Ken Natsuga, Wataru Nishie, James R McMillan, Hiroyuki Nakamura, Daisuke Sawamura, Masashi Akiyama, Hiroshi Shimizu
• Journal: International journal of dermatology (Int J Dermatol) Vol. 50 Issue 4 Pg. 439-42 (Apr 2011) ISSN: 1365-4632 [Electronic] England
• PMID: 21413955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The International Society of Dermatology.

Chemical References

• Bacterial Proteins
• HetF protein, Nostoc punctiforme
• PLEC protein, human
• Plectin

Topics

• Abortion, Therapeutic
• Amniocentesis (methods)
• Bacterial Proteins
• Ectodermal Dysplasia (genetics)
• Epidermolysis Bullosa Simplex (genetics)
• Family Health
• Female
• Fetal Diseases (genetics)
• Genetic Testing (methods)
• Humans
• Male
• Pedigree
• Plectin (genetics)
• Pregnancy